Bøger i Experientia Supplementum serien

The present book is the ideal complement to the practitioner's manual Techniques in Molecular Systematics and Evolution, recently published by the same editors in the Birkhauser MTBM book series.The first part of this book deals with important applications of evolutionary and systematic analysis at different taxonomic levels.

Volume II focuses on the state-of-the-art technologies and applications of various types of sensors. A picture thus emerges of how applications can be expanded in the future and novel markets can be opened up.

It is no longer time-consuming analysis of unknown products, but rather selective identifications of individual forms, modifications and processings, and overall analysis of global protein outputs from cells and tissues in health and disease.

Are demographic and environmental stochas ticity by far more important for the fate of a population or species than genetic stochasticity (genetic drift and inbreeding)?

If it is true that science proceeds from a romantic through a scientific to a technological stage, then research on bird orientation is certainly on its move from its first to its second grade, and recent developments in radiotelemetry and satellite tracking of migrating birds might already indicate the advent of the third stage.

Following an opening chapter by the late Susumu Ohno on paralogues of sex-determining genes, the five best-studied genes essential for early mammalian gonadal development are portrayed in detail: SF-1 and WT1 and their roles in early events in gonadal development, SRY and SOX9 in testis determination, and the anti-testis gene DAX-1.

Myocardial ischemia and subsequent reperfusion of the ischemic myocardium represent complex phenomena encompassing numerous physiological processes.

Improved research methods and new ideas and impulses are therefore urgently needed, both to stimulate the specialized scientists and to supply the concerned citizen with the updated background information necessary to make responsible decisions.

As a consequence, researchers and project managers in the pharmaceutical industry should have a solid knowledge of the more important methods available to drug discovery, because it is the rapidly and intelligently combined use of these which will determine the success or failure of preclinical projects.

This book brings together lmportant work on the structure and function of the dehydrogenases requiring nicotinamide coenzymes. The structure and function of lactate dehydrogen­ ase, alcohol dehydrogenase, and glyceraldehyde 3-phosphate dehydrogenase are compared. These are the relatively simple oligomeric dehydrogenases for which very extensive structural and mechanistic information is available. Kinetic studies are dealt with in general terms, with selected examples. Genetic and structural relationships revealed by primary structure are discussed. General features of the specificity of dehydrogen­ ase reactions are described. The pyridine nucleotide - disulphide oxidoreductases exemplify a type of multicomponent enzyme complex. Lipoamide dehydrogenase, glutathione reductase, and thioredoxin reduct­ ase are described and compared. The fatty acid synthesizing systems of some organ­ isms are nonaggregated, whereas in other organisms they are multienzyme complexes containing, in animal tissues for example, two closely related multifunctional polypeptide chains. The dehydrogenase activities of the fatty acid syn­ thesizing systems afford many points of interest, which are described and discussed. Hydroxymethylglutaryl-CoA reductase occupies a key position in the synthesis of isoprenoid compounds, including cholesterol. It probably occurs in all forms of life; in animal cells it is a microsomal enzyme. Its properties are reviewed.

The 7th International Cyclotron Conference, In addition to 25 invited papers, a total of held in ZUrich from 19-22 August, 1975, was atten 103 papers were submitted for presentation at the ded by 231 registered .

Within each chapter, which is preceded by a list of the sessions featuring the subject, all papers, invited and contributed, whether presented at the Conference or accepted for publication only, have been arranged in some lo gical order.

The highly topical problems of radioprotection will be treated in the following issues of "Experientia" by competent experts in this field. Before printing the papers have been exchanged among the authors to allow them for commenting upon the articles so that a Symposium by Correspondence on Radioprotective Means and Compounds arose. As organizers and editors of this symposium acted A. LOCKER (Vienna) and K. FLEMMING (Freiburg, Br. ). Contents 9 J. D. Chapman and A. P. Reuvers: The Time-Scale of Radioprotection in Mammalian Cells 19 J. Calkins: General Patterns of DNA Repair and their possible Signif­ icance as Necessary Protection from Environmental Radiation Exposure 31 S. Homsey: Protection by Hypoxia and the Effect of Low Oxygen Tensions on Radiosensitivity 45 L. Revesz and B. Littbrand: Radioprotection by Radiosensitizers 53 T. Sugahara, M. Horikawa, M. H. Ikita and N. Nagata: Studies on a Sulfhydryl Radioprotector of Low Toxicity 63 J. M. Yuhas: Systemic Factors Affecting the Radioprotective Effec­ tiveness of Phosphorothioates 71 C. Streffer: Studies on the Mechanism of 5-Hydroxytryptamine in Radioprotection of Mammals 79 K. Flemming: Some Ideas Concerning the Mode of Action of Radio­ protective Agents 87 A. Locker and K. Flemming: Some General Aspects of Radioprotection (A Summary) 9 The Time-Scale of Radioprotection in Mammalian Cells J. D. Chapman* and A. P.

r Convegno Internazionale su ( Aspetti Biologici dell' Elettrochimica» by Prof. G.B. MARINI BETTOLO Istituto Superiore di Sanita, Roma, Italy Sono lieto di porgere il benvenuto a quanti da varie parti del mondo e precisamente da 22 paesi di quattro continenti, sono accorsi qui a Romi!. per partecipare a questa primo Simposio Intemazionale sugli « Aspetti Bio­ logici dell'Elettrochimica », accogliendo l'invito del Comitato Intemazionale di Termodinamica e Cinetica Elettrochimiche e dell'Istituto Superiore di SanitiL L'Istituto Superiore di Sanita., che ha come suo scopo 10 studio e la ricerca per la tutela della sanita. pubblica, ha sempre favorito e promosso gli incontri di scienziati e ricercatori di tutto i1 mondo su temi di interesse attuale ed in rapida evoluzione che attenessero alle ricerche sia di base che applicate nel campo delle scienze biomediche. si sono svolti in questa stessa Questo Simposio fa seguito ad altri che sede, anche essi su temi di viva attualita., dai metodi di produzione di nuovi antibiotici agli aspetti tossicologici dell'impiego degli additivi, ai me­ todi moderni di analisi dei farmaci, al meccanismo delle protezioni dalle radiazioni ionizzanti sulla materia vivente. Tutti questi incontri hanno avuto una comune caratteristica, sia pure nella grande eterogeneita dei temi, quella di riunire cultori e specialisti di varie parti della scienza e della tecnologia per concorrere alla soluzione di un unico problema interdisciplinare.

Cell motility is an important component of many basic physiologic and pathologic processes. Understanding mechanisms of cell motility is therefore essential to the development of new research and clinical approaches in biomedical research. In the early phases of embryogenesis, prepreogrammed morpho­ genetic movement determines normal development. The migration of the neural crest cells, for example, is responsible for the establishment of almost the entire peripheral nervous system, the proper positioning of the epinephrine-secreting cells in the adrenal gland and the deposition of pigment cells in the skin (Newgreen and Erikson, 1986). Any distur­ bance or deviation from this complex migration pattern results in serious malformations. The embryonic cells are stimulated to migrate by internal signals as well as by signals from adjacent cells. Various stimulatory and inhibitory mechanisms are likely to operate during this dynamic process. However, once morphogenesis is achieved, most so­ matic cells tend to remain stationary, and the motile phenotype is dormant. Under certain physiologic and pathologic conditions, however, cells re-express their motile phenotype and migrate. In wound healing and angiogenesis cell migration and proper three-dimensional positioning is critical. Endothelial cell migration following luminal injury is another homeostatic mechanism which helps prevent vascular lesions (Reidy and Silver, 1985; Sholley et aI., 1977; Wong and Gottlieb, 1988). In pathological conditions such as atherosclerosis, smooth muscle cell migration through the internal elastic lamina to the luminal surface may be the initial event leading to the development of the atherosclerotic plaque (Goldberg, 1982).

The recognition of the role of NPY in stimulation of food intake has already resulted in discovery of potent and selective NPY receptor Y-5 antagonists which are in clinical development for obesity while NPY Y1 receptors are targeted for cardiovascular indications.

Aims to understand, from a evolutionary perspective, the impact of stress on biological systems. This work discusses the role of stress in evolutionary change, from stress induced mutations and selection to speciation and evolution at the geological time scale.

Carbonic anhydrase (CA) is a seemingly ubiquitous enzyme of profound physiological importance, which plays essential roles in respiration, acid-base homeostasis, bone resorption, calcification, photosynthesis, several biosynthetic pathways and a variety of processes involving ion, gas and fluid transfer.

It is no longer time-consuming analysis of unknown products, but rather selective identifications of individual forms, modifications and processings, and overall analysis of global protein outputs from cells and tissues in health and disease.

"Stress-Inducible Cellular Responses" are essential for survival of cells of all species under adverse conditions. At the molecular level this is ac­ complished by a number of essential proteins all of which are involved in various aspects of cellular homeostasis through protective or adaptive func­ tions. Interestingly, molecules such as heat shock proteins have properties as molecular chaperones and are involved in multiple stages of a protein biogenesis beginning with synthesis and involvement in the subsequent events of folding, translocation, and degradation. Heat shock proteins have a critical role to stabilize folding intermediates and to prevent protein aggregation. In addition, stress-proteins serve as targets for immune re­ sponses in immune homeostasis and during infections. The term Stress Response reflects the rapid growth and breadth of this field which includes the molecular and cellular response to drugs, UV irra­ diation, oxidative stress, and environmental toxins. Radical scavengers such as superoxide dismutases and inducible regulatory proteins of metall­ ic ion status such as ferritin and protein disulfide isomerases are also con­ sidered within the frame of stress proteins and represent a new and growing class of stress responses.

thrombospondin-l may be encoded by a tumor suppressor gene. Dr. O'Reilly discusses angiostatin, an exciting recently discovered factor derived from the fibrinolytic proenzyme plasminogen that inhibits tumor angiogenesis, primary tumor growth, and formation of metastases. In addition to the soluble class of angiogenesis-regulatory factors discussed above, interactions of endothelial cells with components of the extracellular matrix and with other cell types are critical for proper formation of vessels. Drs. Grant and Kleinman discuss the role of laminin and other matrix molecules in regulation of capillary formation. Dr. van Hinsbergh and colleagues describe the role of fibrin and the fibrinolytic system in angiogenesis associated with wound repair. Cell surface mole­ cules that interact with the extracellular matrix have been implicated in the regulation of angiogenesis. Dr. Varner discusses some exciting new studies on the roles of specific vascular cell integrins (a /33 and a /3s) in mediating v v tumor angiogenesis and angiogenesis associated with wound healing. The pericyte, a vascular smooth muscle-like cell, exerts a powerful regulatory effect during the later stages of angiogenesis in which mature capillaries are formed. These mechanisms are discussed by Drs. Hirschi and D' Amore. With all the recent progress in the molecular biology of angiogenesis, the contribution of microenvironmental conditions such as hypoxia and pH to angiogenesis is often ignored. Drs. Rockwell and Knisely review this area of investigation and present studies of experimental tumor models.

gar discusses recent studies of the SF gene promoter that may be relevant to understanding the detailed molecular mechanism(s) by which soluble factors regulate SF production. Polverini and Nickoloff discuss another mechanism by which SF may enhance tumor growth, ie., stimulation of angiogenesis, the formation of new blood vessels from pre-existing microvessels. Angiogenesis is required for continued growth of most solid tumors, and provides a mechanism by which the stroma may continue to grow along with the tumor cells. Although endothelial cells are stromal cells, they express a number of epithelial characteristics including (i) epithelial-like tight junctions and junctional proteins; (ii) the ability to organize into flat­ tened tubular structures; (iii) the c-met receptor protein; and (iv) biologic responsiveness to SF. It is, perhaps, not surprising that vascular endothe­ lial cells may both produce and respond to SF in different situations. 'Epithelialness' may be defined in two ways: (i) expression of generic epithelial structures and proteins (eg., specialized junctions, junctional proteins [eg., cadherins, ZOl], cytokeratins); and (ii) production of specific differentiated products (eg., milk proteins by mammary epithelia, renin by renal tubular epithelia of the juxtaglomerular apparatus). Recent studies suggest that SF Ic-met signalling may mediate epithelia­ mesenchyme interconversion, in part by modifying some of the generic epithelial characteristics. Nusrat discusses the effects of SF on the epithelial junctional apparatus. Relatively little is known about whether and how SF regulates cell-specific differentiation.

In this volume outstanding specialists review the state of the art in nervous system research for all main invertebrate groups. Novel techniques in molecular and developmental biology are creating new perspectives that point toward a theoretical foundation for a modern organismic biology.

The present book is the ideal complement to the practitioner's manual Techniques in Molecular Systematics and Evolution, recently published by the same editors in the Birkhauser MTBM book series.The first part of this book deals with important applications of evolutionary and systematic analysis at different taxonomic levels.

In modern ecotoxicology, fish have become the major vertebrate model, and a tremendous body of information has been accumulated. This volume attempts to summarize our present knowledge in several fields of primary ecotoxicological interest ranging from the use of (ultra)structural modifications of selected cell systems as sources of biomarkers for environmental impact over novel approaches to monitoring the impact of xenobiotics with fish in vitro systems such as primary and permanent fish cell cultures, the importance of early life-stage tests with fish, the bioaccumulation of xenobiotics in fish, the origin of liver neoplastic lesions in small fish species, immunocytochemical approaches to monitoring effects in cytochrome P450-related biotransformation, the impact of heavy metals in soft water systems, the environmental toxicology of organotin compounds, oxidative stress in fish by environmental pollutants to effects by estrogenic substances in aquatic systems.

Most organisms and populations have to cope with hostile environments, threatening their existence. Their ability to respond phenotypically and genetically to these challenges and to evolve adaptive mechanisms is, therefore, crucial. The contributions to this book aim at understanding, from a evolutionary perspective, the impact of stress on biological systems. Scientists, applying different approaches spanning from the molecular and the protein level to individuals, populations and ecosystems, explore how organisms adapt to extreme environments, how stress changes genetic structure and affects life histories, how organisms cope with thermal stress through acclimation, and how environmental and genetic stress induce fluctuating asymmetry, shape selection pressure and cause extinction of populations. Finally, it discusses the role of stress in evolutionary change, from stress induced mutations and selection to speciation and evolution at the geological time scale. The book contains reviews and novel scientific results on the subject. It will be of interest to both researchers and graduate students and may serve as a text for graduate courses.

receptors containing an integral ionic channel), 2) metabotropic receptors (receptors coupled to G proteins) and 3) voltage-dependent ionic channels (Na+, K + and Ca2+ channels) were already well differentiated when vertebrates separated from invertebrate species.

The 39 chapters in this volume consider subjects ranging from genetics, markers, and molecular biology of alcoholism, to clinical observations and treatment. The aim is to integrate pertinent information from the fields of molecular and cell biology with view to establishing a molecular basis of alcohol use and abuse.